RESILIENT: A Randomized, Open Label Phase 3 Study of Irinotecan Liposome Injection (ONIVYDE®) Versus Topotecan in Patients With Small Cell Lung Cancer Who Have Progressed on or After Platinum-based First-Line Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 491
- 试验地点
- 118
- 主要终点
- Part 1: Number of Participants With Dose-Limiting Toxicities (DLT)
研究概览
简要总结
A randomized, open label phase 3 study of irinotecan liposome injection (ONIVYDE®) versus topotecan in patients with small cell lung cancer who have progressed on or after platinum-based first-line therapy
The study was conducted in two parts:
- Dose determination of irinotecan liposome injection
- A randomized, efficacy study of irinotecan liposome injection versus topotecan
详细描述
The study was conducted in two parts:
Part 1: Open-label dose-finding study of irinotecan liposome injection. 30 patients were planned to be enrolled.
Part 1 Primary Objectives:
- Describe the safety and tolerability of irinotecan liposome injection monotherapy administered every 2 weeks
- Determine the optimal irinotecan liposome injection monotherapy dose for Part 2 of this study
Part 2: A randomized, efficacy study of irinotecan liposome injection versus intravenous (IV) topotecan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age.
- •Able to understand and provide an informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy >12 weeks
- •Histopathologically or cytologically confirmed small cell lung cancer
- •Evaluable disease as defined by RECIST Version 1.1 guidelines (patients with non measurable lesions only are eligible).
- •Radiologically confirmed progression on or after first-line platinum based chemotherapy (carboplatin or cisplatin), or chemo-radiation including platinum-based chemotherapy for treatment of limited or extensive stage Small Cell Lung Cancer (SCLC). In addition to platinum-based regimen, one line of immunotherapy as monotherapy or in combination, in first or in second line setting is allowed.
- •Recovered from the effects of any prior chemotherapy, surgery, radiotherapy or other anti-neoplastic therapy (recovered to Grade 1 or better, with the exception of alopecia, peripheral neuropathy, or ototoxicity).
- •Adequate bone marrow reserves
- •Adequate hepatic function
- •Adequate renal function
- •Electrocardiogram during the Screening period without any clinically significant findings, per investigator's assessment
- •Patients with certain types of asymptomatic CNS metastases that meet ALL the following criteria are eligible.
- •Patients with asymptomatic CNS metastases prior to enrollment
- •Prior radiation for CNS metastatic disease is completed ≥4 weeks prior to enrollment
- •CNS metastases that are stable or have decreased according to the post radiation follow-up scan that is conducted at least 4 weeks after completion of radiation treatment for CNS lesion.
- •Patients have discontinued corticosteroids or are on stable low-dose steroids (prednisone or equivalent 10 mg daily or less) for at least 1 week after completion of radiation for CNS lesion prior to enrollment.
- •Exclusion Criteria
- •Any medical or social condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
- •Pregnant or breast feeding;
- •Patients with large cell neuroendocrine lung carcinoma.
- •Patients who have received prior topoisomerase I inhibitor treatment, retreatment with platinum-based regimen, antibody-drug conjugates or molecular targeted agents, more than one line of immunotherapy, or any other additional regimen of prior cytotoxic chemotherapy.
- •Patients with the symptomatic Central Nervous System (CNS) metastasis and/or who have developed new or progressive brain metastasis within 3 months following prophylactic and/or therapeutic cranial radiation (whole brain stereotactic radiation).
- •Patients with carcinomatous meningitis.
- •Unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week or strong CYP3A4 inducers at least 2 weeks prior to receiving the first dose of irinotecan liposome injection.
- •Have a previous or concurrent cancer that is distinct in primary (non-pulmonary) site or SCLC histology
- •Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is less, prior to the first scheduled day of dosing in this study.
- •Severe cardiovascular and pulmonary diseases
- •New York Heart Association Class III or IV congestive heart failure, ventricular arrhythmias, or uncontrolled blood pressure.
- •Active infection
- •Known hypersensitivity to any of the components of irinotecan liposome injection, other liposomal products, or topotecan.
- •Clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1.
排除标准
- 未提供
研究组 & 干预措施
Part 1: Experimental Arm, dose level 1
Irinotecan liposome injection
干预措施: Irinotecan liposome injection (Drug)
Part 1: Experimental Arm, dose level 2
Irinotecan liposome injection
干预措施: Irinotecan liposome injection (Drug)
Part 2: Experimental Arm
Irinotecan liposome injection
干预措施: Irinotecan liposome injection (Drug)
Part 2: Control Arm
Topotecan
干预措施: Topotecan (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose-Limiting Toxicities (DLT)
时间窗: From the start of the first study treatment administration (Day 1) up to 14 days after the second dose of study treatment administration, a maximum of 42 days
A TEAE was considered as DLT if it occurred during the safety evaluation period (i.e. first 28 days of treatment or 14 days after the second dose of study treatment if there was a treatment delay due to non-DLT related reasons) and were deemed related to the study treatment by the investigator. The determination of whether an Adverse Event was considered a Dose Limiting Toxicity was made by the Safety Review Committee (SRC) comprising the Part 1 Investigators and the Medical Monitor(s) of the Sponsor.
Part 2: Overall Survival (OS)
时间窗: From date of randomization (within 7 days before start of study treatment) until death. Assessed up to Part 2 primary analysis DCO date of 08 February 2022 (approximately 900 days)
The OS was defined as the time from randomization date to the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. The OS was calculated using Kaplan-Meier technique. Following end of treatment participant and/or family was contacted by telephone every month to assess vital status.
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
时间窗: The TEAEs were reported from the time of first study treatment administration (Day 1) up to 30 days after the date of last study treatment administration, approximately 680 days
An adverse event (AE) was any untoward medical occurrence in a participant following or during exposure to a study treatment, whether or not causally related to the study treatment. An undesirable medical condition could be symptoms, signs or abnormal results of an investigation. An SAE was any AE that: resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; resulted in congenital anomaly or birth defect; or was medically important. A TEAE was any AE that occurred or worsened on or after the day of first dose of study treatment and within 30 days after discontinuation of study treatment.
次要结局
- Part 1: Objective Response Rate (ORR)(RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days)
- Part 1: OS(From Baseline (Day 1) until death. Assessed up to Part 1 DCO date of 11 August 2021 (approximately 1177 days))
- Part 2: ORR(RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days)
- Part 2: Median Duration of Response (DoR)(RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days)
- Change From Baseline in EORTC QLQ-LC13 Cough Scale at Week 12(Baseline (Day 1) and Week 12)
- Part 1: Progression-Free Survival (PFS)(RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 1177 days)
- Part 2: PFS(RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days)
- Part 2: Median Time to Objective Response (OR)(RECIST assessments performed at Baseline (within 28 days before start of study treatment), every 6 weeks post first dose and treatment pause, 30 days after discontinuation of study treatment, then every month thereafter, approximately maximum of 900 days)
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)/Lung Cancer Supplement (LC13) Dyspnea Scale at Week 12(Baseline (Day 1) and Week 12)